Nanoceria Aggregate Formulation Promotes Buffer Stability, Cell Clustering, and Reduction of Adherent Biofilm in Streptococcus mutans

Streptococcus mutans is one of the key etiological factors in tooth-borne biofilm development that leads to dental caries in the presence of fermentable sugars. We previously reported on the ability of acid-stabilized nanoceria (CeO 2 -NP) produced by the hydrolysis of ceric salts to limit biofilm adherence of S. mutans via non-bactericidal mechanism(s). Herein, we report a chondroitin sulfate A (CSA) formulation (CeO 2 -NP-CSA) comprising nanoceria aggregates that promotes resistance to bulk precipitation under a range of conditions with retention of the biofilm-inhibiting activity, allowing for a more thorough mechanistic study of its bioactivity. The principal mechanism of reduced in vitro biofilm adherence of S. mutans by CeO 2 -NP-CSA is the production of nonadherent cell clusters. Additionally, dose-dependent in vitro human cell toxicity studies demonstrated no additional toxicity beyond that of equimolar doses of sodium fluoride, currently utilized in many oral health products. This study represents a unique approach and use of a nanoceria aggregate formulation with implications for promoting oral health and dental caries prevention as an adjunctive treatment.